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Molecular Biology

Molecular biology studies the molecular mechanisms of life, particularly those responsible for genes and their expression. In the center of molecular biology are the nucleic acids, DNA and RNA, and how they contribute to the synthesis of proteins.

After a historical introduction (Unit 1), this course describes the basic types of DNA and RNA structure and the molecular interactions that shape them (Unit 2). Unit 3 describes how DNA is packaged within the cellular nucleus as chromosomes; in eukaryotes the DNA coils around histones to form nucleosomes that comprise the chromatin of the chromosomes. The next three units describe the core processes of molecular biology: replication of DNA (Unit 4), transcription of DNA into messenger RNA (Unit 5), and translation of messenger RNA into a protein (Unit 6). These are followed by modifications of these basic processes: regulation of gene expression (Unit 7), DNA mutation and repair (Unit 8), and DNA recombination and transposition (Unit 9). The course concludes with techniques commonly used in molecular biology (Unit 10, 11). These final units are important for anyone evaluating the power of molecular biology.

Primary Resources: This course is composed of a range of different free, online materials. However, the course makes primary use of the following materials:

Requirements for Completion: In order to complete this course, you will need to work through each unit and all of its assigned materials. Please pay special attention to Units 4, 5, and 6, as these lay the groundwork for understanding the more advanced, exploratory material presented in the latter units. You will also need to complete:

Please note that you will only receive an official grade on your final exam. However, in order to adequately prepare for this exam, you will need to work through the problem sets within the above-listed assessments.

In order to pass this course, you will need to earn a 70% or higher on the final exam. Your score on the exam will be tabulated as soon as you complete it. If you do not pass the exam, you may take it again.

Time Commitment: This course should take you a total of 135.5 hours to complete. Each unit includes a “time advisory” that lists the amount of time you are expected to spend on each subunit. These should help you plan your time accordingly. It may be useful to take a look at these time advisories and determine how much time you have over the next few weeks to complete each unit and then set goals for yourself. For example, Unit 1 should take you approximately 10.5 hours to complete. Perhaps you can sit down with your calendar and decide to complete subunits 1.1 and 1.2 (a total of 3.5 hours) on Monday night, subunit 1.3 (a total of 4.5 hours) on Tuesday night, etc.

This course features a number of Khan Academy™ videos. Khan Academy™ has a library of over 3,000 videos covering a range of topics (math, physics, chemistry, finance, history and more), plus over 300 practice exercises. All Khan Academy™ materials are available for free at www.khanacademy.org.

The twisted ladder shape has become the symbol of genetics; it stands for the double stranded DNA. The basic principles of inheritance, the nature of DNA, and its significance in inheritance were all synthesized from experimental findings of scientists who were trained in a variety of disciplines. The inheritance patterns of traits were described without knowing the underlying molecular mechanisms, and the composition of DNA was determined without knowing its significance in inheritance. By 1950, it was determined that DNA is the hereditary material. In 1953, the structure of the DNA was published: the twisted ladder.

Instructions: Please use the DNA Interactive site to learn that our knowledge on inheritance and DNA is very recent. The timeline of some of the great discoveries in DNA research is listed here. It may help you to see these dates together with the time when, for example, color TV, air conditioning, or plastic was invented.

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Instructions: Please watch the video (26 min) for a step-by-step tutorial on using Punnett squares to determine how alleles of more than one gene assort independently. During sexual reproduction both parents pass on some of their traits to their offspring(s). Mendel's law of segregation describes how different versions of one trait are combined in the offspring. Mendel's law of independent assortment describes how different versions of different traits are combined in the offspring. Please make sure that you can predict the genotype and phenotype of the F1 generation using Punnett squares. You may need to follow this video several times. Be patient; it may take some time to get used to the Punnett squares. This is a great tool, used every day in genetic counseling.

Instructions: Please study this page. Morgan published his work on "coupling" in Mendelian genetics in 1911. McClintock published her work on jumping genes in 1951. She used Zea mays (maize) as a model organism.

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Instruction: Please study the "Laying the Groundwork: Levene Investigates the Structure of DNA" section in this publication. You have to navigate to "Page 2" using the "Next Page" link in the right bottom corner of this site. Levene published his work in 1915.

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Instructions: Please study the "DNA Is Identified as the Transforming Principle" section, including Figure 3. Avery and his colleagues published their experiments in 1944. They used Streptococcus pneumoniae as a model organism.

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Instructions: Please study the "DNA Is Identified as the Transforming Principle" section, including Figure 3. Hershey and Chase published their experiments in 1952. They used virus infected Escherichia coli as a model organism.

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Instructions: Please investigate the critical evidence that led to the model of the DNA double helix. Rosalind Franklin’s X-ray diffraction image #51 is shown here. Click on the “Launch interactive” button and advance step by step from image #51 to the double helix model of DNA. Please note that all structural parameters of the double helix are provided by image #51. Franklin and Gosling published the structure of the A-form and B-form of DNA in 1953.

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Unit 2: Nucleic Acids and Proteins: Structure and Function

Nucleic acids and proteins are biopolymers. Nucleic acids are nucleotide polymers, while proteins are amino acid polymers. DNA is a polynucleotide, which typically has double helical 3D structure. RNA is a polynucleotide as well, but its 3D structure is more versatile. Some proteins and some RNA molecules act as biological catalysts and regulate cellular metabolism.

Instructions: Please study the "Native DNA Is a Double Helix of Complementary Antiparallel Chains" and "DNA Can Undergo Reversible Strand Separation" sections on this page. Please note that the B-form is the most common DNA structure. If you read about DNA or dsDNA, then the structure is the B-form unless otherwise indicated. The B-form was discovered by Franklin and Gosling (see unit 1). The DNA strands in the B-form are in antiparallel orientation. A right-handed helix spirals away from the viewer in a clockwise manner.

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Unit 3: Chromosome, Chromatin, and Nucleosome

DNA is packed into chromosomes in cells. The structure of the chromosome is constantly changing based on the metabolic activities within the cell. The degree of chromosome condensation is regulated by protein modifications and by the nucleosome remodeling complex.

Instruction: Please study this page. Please note that eukaryotes have their chromosomes in the nucleus, which is a membrane-bound subcellular organelle. Prokaryotes have no subcellular organelles; their chromosomes are in their cytoplasm.

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Instructions: Please study the "Most Bacterial Chromosomes Are Circular with One Replication Origin," "Eukaryotic Nuclear DNA Associates with Histone Proteins to Form Chromatin," and "Eukaryotic Chromosomes Contain One Linear DNA Molecule" sections on this page. Please note that DNA interacts with basic proteins in the chromosomes; in eukaryotes these proteins are called histones.

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Instructions: Please study the "Chromatin Exists in Extended and Condensed Forms" section on this page, including the "Structure of Nucleosomes" and "Structure of Condensed Chromatin" subsections. Please note that DNA interacts with basic proteins in the chromosomes; in eukaryotes these proteins are called histones.

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Instructions: Please read this publication. Please note that heterochromatin regions are the centromere and the telomeres of a chromosome; heterochromatin is tightly packed. Euchromatin is loosely packed and metabolically active.

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The Saylor Foundation does not yet have materials for this portion of the course. If you are interested in contributing your content to fill this gap or aware of a resource that could be used here, please submit it here.

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Unit 4: DNA Replication

High fidelity characteristics of DNA replication ensure that cell proliferation results in genetically identical daughter cells. DNA polymerases synthesize a complement strand on the template strand, but the cooperation of many other proteins is needed as well. First the strands of the dsDNA must be separated, and then a primer should be provided before the DNA polymerase can start to work. DNA polymerase continuously copies one strand of the dsDNA, but the complement is copied in pieces and must be ligated. Circular dsDNA replicates to two identical dsDNA. Linear dsDNA becomes shorter with each round of replication, because DNA polymerases have only 5'–>3' activity and cannot replace RNA primers. This is why telomere regions become shorter and shorter during aging.

Instructions: Please study the following sections: "An RNA Primer Synthesized by Primase Enables DNA Synthesis to Begin;" "One Strand of DNA Is Made Continuously, Whereas the Other Strand Is Synthesized in Fragments;" "DNA Ligase Joins Ends of DNA in Duplex Regions;" "DNA Replication Requires Highly Processive Polymerases;" "The Leading and Lagging Strands Are Synthesized in a Coordinated Fashion;" and "DNA Synthesis Is More Complex in Eukaryotes than in Prokaryotes." In prokaryotes, DNA synthesis takes place in the cytoplasm; in eukaryotes, DNA synthesis takes place in the nucleus.

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Instructions: Please study the "The Replication Fork" section on this page. Please note that the DNA synthesis on the lagging strand results in short DNA segments with RNA at their 5' end: These are the Okazaki fragments. These fragments are linked to each other by the DNA ligase enzyme after the RNA is replaced by DNA.

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Instructions: Please study the "Telomeres Are Unique Structures at the Ends of Linear Chromosomes" and "Telomeres Are Replicated by Telomerase, a Specialized Polymerase That Carries Its Own RNA Template" sections on this page. Please notice that only linear chromosomes have telomere regions. Also, telomere regions become shorter as the cell grows older.

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Unit 5: Transcription

Transcription leads to the synthesis of a complementary RNA strand from a DNA template. The process is less precise than DNA replication, since RNA polymerases do not have proofreading activity. There are remarkable differences between prokaryotic and eukaryotic transcription, which we will discuss in detail in Unit 7 (Regulation of Gene Expression). The turnover of RNA molecules is commonly regulated by P-bodies and miRNA in the cell. This unit focuses on mRNA and miRNA; tRNA and rRNA are discussed in the next unit.

Instructions: Please study the following sections: "An RNA Primer Synthesized by Primase Enables DNA Synthesis to Begin;" "One Strand of DNA Is Made Continuously, Whereas the Other Strand Is Synthesized in Fragments;" "DNA Ligase Joins Ends of DNA in Duplex Regions;" "DNA Replication Requires Highly Processive Polymerases;" "The Leading and Lagging Strands Are Synthesized in a Coordinated Fashion;" and "DNA Synthesis Is More Complex in Eukaryotes Than in Prokaryotes."

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Instruction: Please study the introduction and "Three Eukaryotic Polymerases Catalyze Formation of Different RNAs" sections on this page. Please note that these three RNA polymerases have different specificity, thus they cannot replace each other.

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Instructions: Please study the "Synthesis of Bacterial mRNAs" section on this page. Translation and transcription take place simultaneously in prokaryotes. Please note that prokaryotic mRNAs are not processed.

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Instructions: Please study the "Synthesis of Eukaryotic mRNAs by RNA Polymerase II" section on this page, including the "Capping of RNA Polymerase II Transcripts Occurs Immediately after Initiation," "Elongation of Eukaryotic mRNAs," and "Termination of mRNA Synthesis Is Combined with Polyadenylation" subsections. In eukaryotes, transcription follows translation, and transcription and translation take place in different subcellular compartments. Please note that eukaryotic mRNAs are processed with a 5'-cap and 3'-tail. Capping and polyadenylation are post-translational modifications.

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Instructions: Please study the "Intron Splicing" section on this page, including the following subsections: "Conserved Sequence Motifs Indicate the Key Sites in GU-AG Introns," "Outline of the Splicing Pathway for GU-AG Introns," "snRNAs and Their Associated Proteins Are the Central Components of the Splicing Apparatus," "Alternative Splicing Is Common in Many Eukaryotes," and "AU-AC Introns Are Similar to GU-AG Introns but Require a Different Splicing Apparatus." Differential splicing results in multiple RNA molecules from one gene. In differentially spliced RNAs, different exon combinations are spliced together. Exon(s) may correspond to protein domains, thus the characteristics of the encoded protein become predictable from the combination of the functional domains.

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Instruction: Please study this page, including the figures embedded into the publication. Please note that binding of metabolites to riboswitches regulates the expression of the mRNA wherein the riboswitch is located.

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Instructions: Please watch this video (35 min). Please note that P-bodies serve as a scaffolding center for miRNA, and translationally repressed mRNAs are also stored in P-bodies.

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Unit 6: Protein Synthesis and the Genetic Code

Protein synthesis is the translation of nucleic acid sequence to protein sequence. The nucleic acid sequence is read in triplets; each triplet codes for only one amino acid. The genetic code is said to be universal, since a mRNA is translated into the same protein in a variety of distantly related organisms. Protein synthesis takes place in the cytosol on free ribosomes and on rough ER-bond ribosomes.

Instructions: Please scroll down to the "Exceptions to the Code" section and study the text until the end of the page. Please note that these are just a few examples when the standard genetic code is violated.

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Instruction: Please study the "Membrane-Bound Ribosomes Define the Rough ER" section this page. Please note that there are free ribosomes and bound ribosomes. All ribosomes start as free ribosome. A ribosome that translates a protein with an N-terminal ER signal peptide will move to the ER and will become a bound ribosome.

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Unit 7: Regulation of Gene Expression

The synthesis of a complementary RNA strand from a DNA template takes place in somewhat different ways in prokaryotes and in eukaryotes, as you learned in Unit 5. In this unit you will study gene expression in more detail. Synchronized gene expression on prokaryotes is directed in operons, wherein certain genes that are next to each other are regulated by the binding or not binding of a repressor to an upstream region. In the case of eukaryotes, transcription is synchronizing expression of genes that are scattered throughout the chromosome(s). In eukaryotes, genes are expressed only if a set of enhancers are present and a complex transcription initiation complex can form. This can lead to tissue- and activity-specific gene expression, when distant genes express the same set of enhancers. Epigenetics means "in addition to" genetics, and it is studying why genes with identical sequences are expressed differently. Epigenetic changes are chemical modifications (not sequence changes) that living organisms pick up during their life as a response to environmental stimuli, e.g., nutrition. The result is turning genes off and on, through making the chromosomal structure more or less compact. The more compact structure interferes with gene transcription.

Instruction: Please study the "RNA Polymerase and Transcription" section on this page. Please note that in prokaryotes, the genes that should be expressed at the same time are often located next to each other.

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Instruction: Please study the "Repressors and Negative Control of Transcription" and "Positive Control of Transcription" sections on this page. Please note that the repressor inhibits transcription unless it is inactivated by the inducer. The inducer is allolactose for Lac operon. Inducible operons are common in the regulation of catabolic pathways.

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Instruction: Please complete this problem set. There are 14 problems in the set, and each problem is linked to a brief tutorial page. After answering a question, please click on and study each tutorial page as well.

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Instruction: Please study the "Transcriptional Attenuation" section on this page. Please note that the repressor cannot interfere with transcription unless it is activated by the co-repressor. The co-repressor is tryptophan for Trp operon. Repressible operons are common in the regulation of anabolic pathways.

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Instruction: Please study the introduction and "Most Genes in Higher Eukaryotes Are Regulated by Controlling Their Transcription" sections on this page. Please note that while their genomic DNAs are identical, different cell types are expressing different proteins in eukaryotes.

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Instruction: Please study the "Regulatory Elements in Eukaryotic DNA Often Are Many Kilobases from Start Sites" section on this page. Please note that in eukaryotes, the genes that should be expressed at the same time are often far from each other on the chromosome.

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Instruction: Please complete this problem set. There are 13 problems in the set, and each problem is linked to a brief tutorial page. After answering a question, please click on and study each tutorial page as well.

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Instruction: Please study this page. Epigenetics refers to anything that changes gene expression without changing the DNA sequence of the genome. These changes are chemical modifications, e.g., DNA methylation and histone acethylation. Epigenetic changes turn genes on and off in the genome.

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Instruction: Please study this page. Please note that epigenetic changes respond quickly to environmental stimuli, e.g., famine and substances in our food. Research shows that epigenetic changes can be inherited.

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Unit 8: DNA Mutation and Repair

DNA mutation is a permanent change in the DNA sequence. Such a change may be neutral or good or bad for the cell. A mutation is neutral if it does not affect the expression or function of any gene product. Rarely, it is good if it brings advantage for the organism or for the offspring of the organism. Sometimes it is bad if it is disadvantageous, e.g., if it results in cancer or other disease. DNA polymerases have proofreading activity and work to keep the DNA unchanged. There are cellular defense mechanisms in multi-cellular organisms, e.g., programmed cell death, which work toward eliminating mutated cells. You can learn about programmed cell death in BIO402: Pathobiology or BIO404: Cancer Biology courses in the Biology Program. In general, mutations may arise from two sources: internal mistakes in gene replication or external mutagens.

Instruction: Please study the "Recombinational Repair" section on this page.

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Unit 9: DNA Recombination and Transposition

Recombination and transpositions permanently alter DNA sequences. Recombination contributes to DNA repair and it increases genetic variation. Transposition events also increase genetic variation, and they can result in new domain combinations in proteins through exon shuffling.

Instruction: Please study the "Exon Shuffling Permits Diverse Combinations of Structure and Functional Modules, and May be Mediated by Transposable Elements" section on this page. Please note that exon shuffling brings together functional domains of unrelated genes, thus it can create novel proteins with unique regulatory features.

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Unit 10: Techniques

The classical core technique in molecular biology is cloning. The cloned DNA is usually recombinant DNA, wherein a plasmid DNA and the gene of interest are pieced together. Techniques to amplify, analyze, and mutate DNA are also discussed here. Please take the BIO403: Biotechnology course if you would like to learn more about the array of techniques employed in molecular biology.

Instructions: Please study "The Size and Subunit Composition of a Protein Can Be Determined by SDS Polyacrylamide-Gel Electrophoresis" and "More Than 1000 Proteins Can Be Resolved on a Single Gel by Two-dimensional Polyacrylamide-Gel Electrophoresis" sections on this page.

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Instructions: Please study the "Selective Cleavage of a Protein Generates a Distinctive Set of Peptide Fragments" and "Mass Spectrometry Can Be Used to Sequence Peptide Fragments and Identify Proteins" sections on this page.

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Instruction: Please complete this problem set. There are 11 problems in the set, and each problem is linked to a brief tutorial page. After answering a question, please click on and study each tutorial page as well.

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Unit 11: Model Organisms

Many model organisms are used in molecular biology, both in research and in biotechnology. They help to answer questions on the function of the genes, and they can be engineered to produce a variety of substances. The simplest of all is E. coli, the working horse of any cloning protocol. C. elegansand D. melanogaster taught us the function of many genes. A. thaliana has been widely employed in GMO plan pilot experiments. As a general rule, always the simplest possible model organism is employed for a certain task. If post-translational modification is not essential, then proteins can be produced in E. coli, but a eukaryotic model organism is the right choice if post-translational modification is essential. You can see an array of applications if you take the BIO403: Biotechnology course.

Instructions: Please watch the video (24 min) for an overview of viruses. Bacteriophages are viruses that infect only bacteria. Viruses are in the grey zone between life and the non-living world. A virus can multiple only in its specific host cell, while it takes over the host's metabolic activities. The host range describes the cells that can be infected by a certain virus. Viruses may destroy their host in a lytic cycle or incorporate themselves into the host's genome. Viruses are used in a broad range of biotechnology applications, including gene therapy and phage therapy.

Instructions: You must be logged into your Saylor Foundation School account in order to access this exam. If you do not yet have an account, you will be able to create one, free of charge, after clicking the link.